Transcript How Basic Research on Early Experience and Stress Bears on

Early Experience, Stress and Neurobehavioral
Development Center
NIMH Interdisciplinary Development
Science Center
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How do early life events get “under the skin”
to impact long-term mental and physical
health outcomes?
Understanding the mechanisms should
facilitate:
◦ Identifying targets for intervention/prevention
efforts
 Who is most vulnerable
 Conditions to target
 Sensitive Periods
◦ Assessing effectiveness of intervention/prevention
efforts
Acute - enhances immune,
Memory, energy replenishment,
Cardiovascular function
Chronic - suppresses immune,
Memory, promotes bone
Mineral loss, muscle wasting;
Metabolic syndrome
Summary of CRF Functions
STRESS
Immune Function
Reproduction
ACTH
Slow Wave Sleep
Eating
Self Grooming
Despair
Neophobia
[novel environ]
Hyperlocomotion
Catecholamines
[familiar environ]
Kindling
Glucocorticoids
s
s
s
s
Gluconeogenesis
Lipolysis
Proteolysis
Insulin Resistance
Inflammation
s
s
s
Blood Pressure
Heart Rate
Blood Sugar
GI Blood Flow
LC unit activity
Negative………………Positive
Goldilock’s Principle: Inverted U Relationships
With Health Promoting/Threatening Effects
Promotive Effects
Suppressive Effects
CORT Levels Increasing--->
Diurnal Cortisol Rhythm
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Low Maternal Care
◦ Higher and more
prolonged CORT responses
in adulthood
◦ Higher CRF activity
◦ Higher brain NE activity
◦ Less Brain production of
stress modulators: e.g
natural opiates
◦ More fearful/anxious
behavior
◦ Poorer memory; effects on
learning/memory systems
Maternal Care in Rodents
Adult Outcomes of Poor
Maternal Care
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Epigenesis: Silencing of genes in particular tissues
◦ methylation and histone acetylation;
◦ gene cannot interact with its environment
◦ can’t transcribe code for its protein
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Low Maternal Care Reduced expression of
 GR gene involved in regulating CORT (Meaney and Szyf)
 BDNF gene in PFC (Roth/Sweatt)
 Estrogen Receptor Gene (Champagne)
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Rats Only?
◦ Adult suicide victims: stress-regulating gene silencing in
same brain region as rodent studies IF suicide+child
abuse; not suicide w/o child abuse
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Does parental care buffer stress biology early
in life?
Are neglect and abuse associated with
atypical patterns of stress hormone
production and regulation?
Is a signature of ELS observed among adults
with these experiences?
Do interventions that foster better behavioral
adaptation shift functioning of the CORT
system?
Percent of Children
Adoption
Foster: Dozier
Foster: Fisher
Atypical Patterns Soon After Placement
Toddlers and Preschoolers
Early Abuse + Anxious/Depressive Symptoms
7-12 Year Old Children
Cicchetti, Rogosch and Gunnar, 2009
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First 3 months of life: CORT production and
regulation is extremely sensitive to variations in
parental care
Blair et al: Thousand low income babies: maternal
behavior at 7 mos trumps income/needs ratio in
predicting CORT reactivity at 7 months and in
predicting 15 months CORT regulation and
Attention.
By 2nd year of life: infants in secure attachment
relationships show no increase in CORT when
frightened/distress; insecure do and attachment
disordered infant have chronic high CORT.
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Number of studies now (Heim, Carpenter,
Elzinga)
Adults with Depression+Early Abuse/Neglect:
Hyper-Activity
Adults with No Depression+Early
Abuse/Neglect: Hypo-Activity
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Dozier: Attachment and Biobehavioral Catchup Intervention with Infants in Foster Care
Train foster parents to support the
attachment and regulatory needs of
neglected/abused infants and toddlers
Proof of principle study
◦ Infants/Toddlers in Foster Care
 Randomized to Treatment and Control
◦ Comparison Group of Same Low SES
ABC
DEF
Comparison
0.9
0.8
0.7
Cortisol ug/dl
Salivary Cortisol Levels
1
0.6
*
0.5
0.4
0.3
0.2
0.1
0
AM
PM
Time of Day
Dozier, M et al., 2006, Journal of Social
Issues, 62, 767-785.
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Fisher: Multi-dimensional Treatment Program
◦ Training Foster Parents to Manage Behavior
Problems in supportive, consistent fashion
◦ 24/7 support line for foster parents
◦ Maintaining Consistency of Care and Plan for
Transitions
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Tracking Diurnal Cortisol Rhythm; focus on
amelioration and/or prevention of disruption
on normal daily pattern
1 mo post placement
Fisher, P. A.(2007).
Psychoneuroendocrinology, 32, 892-905.
12 mo post placement
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How does early life stress “get under the skin”
to affect life-long health?
◦ HPA axis may provide one mechanism
◦ Gene by Experience Effects Likely
◦ Experience and epigentic processes
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Measures of stress neurobiology sensitive to
early intervention